Darolutamide 300mg tablets

BackgroundDarolutamide is the next-generation androgen receptor inhibitor approved for the treatment of advanced prostate cancer, including non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). However, the efficacy and safety of darolutamide are nonetheless worthy of further clinical studies. The objective of this meta-analysis was to evaluate the overall survival, metastasis-free survival and various specific adverse events of darolutamide combination therapy in patients with mHSPC or nmCRPC.MethodsThis meta-analysis was performed on PubMed, EMBASE, Web of Science, ClinicalTrials.gov, and the Cochrane Library for English-language articles to collect randomized clinical trials of darolutamide combination therapy in mHSPC and nmCRPC from the start of the database to 15 January 2026. The primary efficacy outcomes were overall survival and metastasis-free survival. Key safety outcomes included the total number of overall adverse events, the total number of grade ≥3 adverse events and serious adverse events, and the occurrence of specific adverse events of interest. The risk of bias was assessed by the Cochrane risk-of-bias tool for randomized trials (RoB 2). Publication bias was assessed by funnel plots.ResultsThere were 8 research articles from 3 randomized clinical trials with 3,483 patients involved in this meta-analysis, including 1,509 nmCRPC patients from the ARAMIS trial, 1974 mHSPC patients from the ARASENS and ARANOTE trials. Combining darolutamide with ADT significantly prolonged overall survival (OS) and metastasis-free survival (MFS) in nmCRPC patients compared with placebo plus ADT. And darolutamide plus ADT with or without docetaxel also showed favorable overall survival in mHSPC patients. Subgroup meta-analyses of OS among mHSPC patients for baseline total PSA (tPSA) values and Gleason scores showed the beneficial efficacy of darolutamide in mHSPC. The addition of darolutamide in ADT and/or docetaxel did not lead to serious adverse events, like heart failure, bone fracture and hypertension, in both nmCRPC and mHSPC patients.ConclusionDarolutamide combination therapy was beneficial to the prognosis and demonstrated a favorable safety profile in patients with advanced prostate cancer.Systematic review registrationIdentifier CRD420251145736.

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ObjectiveAndrogen receptor pathway inhibitors (ARPIs) have revolutionized prostate cancer treatment, but their cardiovascular safety profile requires comprehensive evaluation. This meta-analysis aims to examine the association between ARPI use and hypertension risk in prostate cancer patients.MethodsWe systematically searched PubMed, Web of Science, and ClinicalTrials.gov for randomized controlled trials comparing ARPIs with control. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models for all-grade and grade ≥ 3 hypertension. Subgroup analyses were performed by individual ARPI agents and combination therapies.ResultsTwenty-two studies (derived from 21 distinct randomized controlled trials) involving 22,420 patients were included for analysis. ARPIs significantly increased the risk of all-grade hypertension (RR 1.82, 95% CI 1.51-2.21, p ConclusionARPI treatment significantly increases hypertension risk in prostate cancer patients, with substantial variability among specific agents and regimens. Combination therapy poses the highest risk, while darolutamide demonstrated a lower risk profile in this indirect comparison. These findings support routine blood pressure monitoring and aggressive management in patients receiving ARPI therapy, particularly those with pre-existing cardiovascular risk factors.

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BackgroundNovel hormonal therapies (NHTs) have substantially improved outcomes in prostate cancer across multiple disease states. However, their hepatic safety remains clinically relevant because treatment is often prolonged and may be combined with androgen-deprivation therapy, corticosteroids, or chemotherapy. We performed a systematic review and meta-analysis to quantify the risk of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations associated with NHT-based therapy.MethodsThis study was conducted in accordance with PRISMA guidelines. Randomized controlled trials comparing NHT-containing regimens with control regimens in patients with prostate cancer were eligible if they reported extractable ALT and/or AST adverse-event data. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for four prespecified outcomes: all-grade ALT elevation, grade ≥ 3 ALT elevation, all-grade AST elevation, and grade ≥ 3 AST elevation.ResultsTen randomized studies reported in 11 publications were included, involving 10,173 participants treated with abiraterone, enzalutamide, darolutamide, or abiraterone plus enzalutamide combination regimens. Compared with controls, NHT-based therapy significantly increased the risk of all-grade ALT elevation (RR 1.49, 95% CI 1.12-2.00; I2 = 82.8%), grade ≥ 3 ALT elevation (RR 5.91, 95% CI 2.86-12.20; I2 = 67.5%), all-grade AST elevation (RR 1.58, 95% CI 1.02-2.45; I2 = 84.5%), and grade ≥ 3 AST elevation (RR 3.32, 95% CI 2.13-5.18; I2 = 0%). Subgroup analyses suggested that the hepatic safety signal was more evident for abiraterone-containing and abiraterone plus enzalutamide combination regimens, whereas estimates for enzalutamide and darolutamide varied across outcomes and should be interpreted cautiously because of the limited number of available comparisons.ConclusionsNHT-based therapy for prostate cancer was associated with an increased risk of hepatic enzyme abnormalities, particularly severe ALT elevation. The hepatic safety signal appeared more evident for abiraterone-containing and combination regimens, whereas drug-specific estimates for enzalutamide and darolutamide remained limited. Because this analysis focused on laboratory-defined ALT and AST elevations, careful liver function monitoring remains warranted during NHT-based therapy, especially in patients receiving abiraterone-containing or prolonged combination regimens.

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Androgen receptor pathway inhibitors (ARPIs) combined with androgen deprivation therapy (ADT) have transformed the management of metastatic hormone-sensitive prostate cancer (mHSPC). However, no head-to-head randomised controlled trials (RCTs) have directly compared ARPIs. This study compared the impact of darolutamide plus ADT versus other doublet ARPIs on patient-reported health-related quality of life (HRQoL) outcomes in men with mHSPC using a network meta-analysis (NMA) of RCTs. A Bayesian proportional hazards NMA was conducted using the Bayesian generalised linear model framework to compare time to deterioration in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score using data from the ARANOTE, ARCHES, TITAN, and LATITUDE studies. Darolutamide plus ADT showed a meaningful difference in delaying time to deterioration in FACT-P total score versus ADT (hazard ratio [HR] 0.76, 95% credible interval [CrI] 0.61-0.94) and apalutamide plus ADT (HR 0.74 [95% CrI 0.56-0.99]). Darolutamide plus ADT demonstrated numerically favourable effects compared with abiraterone plus ADT (0.89 [95% CrI 0.69-1.16]) and enzalutamide plus ADT (0.79 [95% CrI 0.60-1.04]), although there was no evidence of a difference. Across treatments, darolutamide plus ADT had the highest probability of being the most effective treatment for delaying deterioration in HRQoL. These findings suggest that darolutamide plus ADT may maintain HRQoL longer than other ARPIs and support darolutamide plus ADT as a patient-centred treatment option.

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